hydroxychloroquine chemoprophylaxis for covid-19 infection in high-risk healthcare workers.

Conditions: SARS-CoV-2; Healthcare Workers

Summary: healthcare personnel are at an increased risk of exposure to sars-cov-2 infection while handling such patients. currently, there is no treatment available for sars-cov-2 and stringent preventive measures are advised to avoid or minimize risk of exposure to healthcare workers. there are in vitro studies available which show inhibition of corona virus by hydroxychloroquine, a widely-used agent against malaria and certain autoimmune conditions and of low-cost and limited toxicity. however, evidence regarding its effects in patients is limited. we plan to conduct a randomized controlled trial to evaluate the safety and potential prophylactic efficacy of hydroxychloroquine in preventing secondary sars-cov-2 infection among healthcare workers at high-risk of exposure while managing such patients.

an interventional randomised control trial that will include 374 participants who will be healthcare workers at variable risks of exposure to sars-cov-2 while managing patients both suspected and confirmed with covid-19 infection.each participant will undergo detailed clinical evaluation to confirm eligibility, complete blood count, retinal imaging and ecg rhythm lead at baseline. a nasopharyngeal swab for reverse-transcriptase-polymerase chain reaction (rt-pcr) will also be taken. the enrolled participants will be randomised to two treatment arms with the experimental arm receiving tab.hydroxychloroquine (hcq) 400mg twice a day on day 1 followed by 400mg weekly for 11 weeks. the placebo comparator arm will receive 2 tablets twice daily on day 1 followed by 2 tablets weekly for 11 weeks. the participants will be followed up via phone call weekly to ensure drug compliance, occurrence of drug-related side effects or respiratory symptoms. the final visit 4 will mark the end of study at 12 weeks from randomisation when a repeat nasopharyngeal swab for sars-cov-2 rt-pcr will be taken.the primary outcome measures will be prevention of sars-cov-2 infection as determined by a negative rt-pcr in the experimental arm at the end of 12 weeks and hcq safety as determined by occurrence of adverse events.

Eligibility criteria:
inclusion criteria: * adult healthcare workers all genders ≥ 18 to ≤ 60 years of age upon study consent. * healthcare workers (doctors and nurses) at services hospital, lahore considered work at high-risk of sars-cov-2 exposure (defined below): * healthcare workers in corona triage areas. * healthcare workers in corona isolation units. * healthcare workers in corona icus. * healthcare workers in general medical wards. * healthcare workers in general surgical wards. * healthcare workers in other units not directly dealing with suspected corona patients e.g. endocrinology department * afebrile with no constitutional symptoms. * no household contact with confirmed active sars-cov-2 infection in the last 3 weeks. * negative pcr at visit 0. * willing and able to comply with scheduled visits, treatment plan, and other study procedures. * willing to not take any other medicines especially fluoroquinolones and macrolides for the duration of study. * signed informed consent, demonstrating that the subject understands the interventions required for the study and the purpose of the study. exclusion criteria: * participation in other investigational clinical trials for the treatment or prevention of sars-cov-2 infection within 30days. * subjects unwilling to practice at least one highly effective method of birth control for the duration of the study. * having a prior history of blood disorders such as aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia or prior history of glucose-6-phosphate dehydrogenase (g-6-pd) deficiency. * having h/o skin disorders e.g. dermatitis, psoriasis or porphyria. * taking any of the following medication: * anti-arrythmic agents including digoxin. * gi drugs including antacids, proton-pump inhibitors, cimetidine. * anti-cancer treatment including methotrexate, cyclosporin. * anti-diabetic agents including insulin. * corticosteroids. * drugs causing qt interval prolongation especially antidepressants, anti-epileptics and macrolides. * drugs affecting electrolyte balance including diuretics, laxatives. * drug allergies: 4-aminoquinolines. * pre-existing retinopathy/maculopathy of the eye. * known chronic liver disease or cirrhosis, including hepatitis b and/or untreated hepatitis. * previous history of severe hypoglycaemia. * known case of renal disease. * untreated or uncontrolled active bacterial, fungal infection. * known or suspected active drug or alcohol abuse. * women who are pregnant or breastfeeding. * known hypersensitivity to any component of the study drug. * a known history of prolonged qt syndrome or history of additional risk factors for arrythmias (e.g., heart failure, family history of long qt syndrome). * known h/o respiratory disorders e.g. asthma, chronic obstructive pulmonary disease.

Keywords: sars-cov-2 hcq prophylaxis healthcare workers